Dietary squalene supplementation improvesDSS-induced acute colitis by downregulating p38 MAPKand NFkB signaling pathways

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Scope:Squalene is a polyunsaturated triterpene, which has exhibited anticancer and antioxidantactivities among others. We investigated dietary squalene supplementation effect on an acutecolitis model induced by dextran sulfate sodium (DSS) in C57BL/6 mice.Methods and results:Mice were fed from weaning with squalene at 0.02% and 0.1%. After4 weeks, mice were exposed to 3% DSS for 5 days developing acute colitis. After DSS removal(5 days), colons were histological and biochemically processed. Our results showed that dietarysqualene treatment exerts anti-inflammatory action in DSS-induced acute colitis. Western blotrevealed that squalene downregulated COX-2 (where COX is cyclooxygenase) and induciblenitric oxide synthase system by inhibition of mitogen-activated protein kinase p38 and thenuclear factor-kappa B signaling pathways, preventing an increase in the cytokines levels.Under our experimental conditions, STAT3 and FOXP3 (where FOXP3 is forkhead box P3)were not modified and the transcriptional regulation of antioxidant and/or detoxifying enzymes,Nrf2 (where Nrf2 is nuclear factor (erythroid-derived 2)-like 2), was reduced in DSS-inducedcolitis. However, any change could be observed after squalene supplementation.Conclusion:Squalene was able to improve the oxidative events and returned proinflammatoryproteins expression to basal levels probably through p38 mitogen-activated protein kinase andnuclear factor-kappa B signaling pathways. However, supplementary studies are needed inorder to provide a basis for developing a new dietary supplementation strategy.

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